Despite major improvements in patient management, the prognosis for patients with lung cancer remains dismal. As our knowledge of the molecular biology of cancers has increased, new targets for therapeutic interventions have been identified. In this article, we discuss some of the more recent developments in this field. They include revisiting some of the established concepts, such as retinoid metabolism and the inhibition of cyclooxygenase-2 metabolism. In addition, newer targets, such as transforming growth factor-β signaling, Janus-activated kinase/signal transducers and activators of transcription pathway, and cell invasion are discussed. These studies demonstrate that multiple, often overlapping, mechanisms of disruption are present in lung cancer cells, presenting a plethora of molecular targets.